1cm8: Difference between revisions

Revision as of 13:07, 21 February 2008

PHOSPHORYLATED MAP KINASE P38-GAMMA

OverviewOverview

BACKGROUND: Mitogen-activated protein (MAP) kinases mediate the cellular response to stimuli such as pro-inflammatory cytokines and environmental stress. P38gamma is a new member of the MAP kinase family, and is expressed at its highest levels in skeletal muscle. P38gamma is 63% identical in sequence to P38alpha. The structure of P38alpha MAP kinase has been determined in the apo, unphosphorylated, inactive form. The structures of apo unphosphorylated ERK2, a related MAP kinase, and apo phosphorylated ERK2 have also been determined. RESULTS: We have determined the structure of doubly phosphorylated P38gamma in complex with an ATP analog by X-ray crystallography. This is the first report of a structure of an activated kinase in the P38 subfamily, and the first bound to a nucleotide. P38gamma residue phosphoryl-Thr183 forms hydrogen bonds with five basic amino acids, and these interactions induce an interdomain rotation. The conformation of the activation loop of P38gamma is almost identical to that observed in the structure of activated ERK2. However, unlike ERK2, the crystal structure and solution studies indicate that activated P38gamma exists as a monomer. CONCLUSIONS: Interactions mediated by phosphoryl-Thr183 induce structural changes that direct the domains and active-site residues of P38gamma into a conformation consistent with catalytic activity. The conformation of the phosphorylation loop is likely to be similar in all activated MAP kinases, but not all activated MAP kinases form dimers.

About this StructureAbout this Structure

1CM8 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

The structure of phosphorylated p38gamma is monomeric and reveals a conserved activation-loop conformation., Bellon S, Fitzgibbon MJ, Fox T, Hsiao HM, Wilson KP, Structure. 1999 Sep 15;7(9):1057-65. PMID:10508788

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OCA

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 ==Overview==
-BACKGROUND: Mitogen-activated protein (MAP) kinases mediate the cellular, response to stimuli such as pro-inflammatory cytokines and environmental, stress. P38gamma is a new member of the MAP kinase family, and is, expressed at its highest levels in skeletal muscle. P38gamma is 63%, identical in sequence to P38alpha. The structure of P38alpha MAP kinase, has been determined in the apo, unphosphorylated, inactive form. The, structures of apo unphosphorylated ERK2, a related MAP kinase, and apo, phosphorylated ERK2 have also been determined. RESULTS: We have determined, the structure of doubly phosphorylated P38gamma in complex with an ATP, analog by X-ray crystallography. This is the first report of a structure, of an activated kinase in the P38 subfamily, and the first bound to a, nucleotide. P38gamma residue phosphoryl-Thr183 forms hydrogen bonds with, five basic amino acids, and these interactions induce an interdomain, rotation. The conformation of the activation loop of P38gamma is almost, identical to that observed in the structure of activated ERK2. However, unlike ERK2, the crystal structure and solution studies indicate that, activated P38gamma exists as a monomer. CONCLUSIONS: Interactions mediated, by phosphoryl-Thr183 induce structural changes that direct the domains and, active-site residues of P38gamma into a conformation consistent with, catalytic activity. The conformation of the phosphorylation loop is likely, to be similar in all activated MAP kinases, but not all activated MAP, kinases form dimers.
+BACKGROUND: Mitogen-activated protein (MAP) kinases mediate the cellular response to stimuli such as pro-inflammatory cytokines and environmental stress. P38gamma is a new member of the MAP kinase family, and is expressed at its highest levels in skeletal muscle. P38gamma is 63% identical in sequence to P38alpha. The structure of P38alpha MAP kinase has been determined in the apo, unphosphorylated, inactive form. The structures of apo unphosphorylated ERK2, a related MAP kinase, and apo phosphorylated ERK2 have also been determined. RESULTS: We have determined the structure of doubly phosphorylated P38gamma in complex with an ATP analog by X-ray crystallography. This is the first report of a structure of an activated kinase in the P38 subfamily, and the first bound to a nucleotide. P38gamma residue phosphoryl-Thr183 forms hydrogen bonds with five basic amino acids, and these interactions induce an interdomain rotation. The conformation of the activation loop of P38gamma is almost identical to that observed in the structure of activated ERK2. However, unlike ERK2, the crystal structure and solution studies indicate that activated P38gamma exists as a monomer. CONCLUSIONS: Interactions mediated by phosphoryl-Thr183 induce structural changes that direct the domains and active-site residues of P38gamma into a conformation consistent with catalytic activity. The conformation of the phosphorylation loop is likely to be similar in all activated MAP kinases, but not all activated MAP kinases form dimers.
 ==About this Structure==
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 [[Category: Single protein]]
 [[Category: Bellon, S.]]
-[[Category: Fitzgibbon, M.J.]]
+[[Category: Fitzgibbon, M J.]]
 [[Category: Fox, T.]]
-[[Category: Hsiao, H.M.]]
+[[Category: Hsiao, H M.]]
-[[Category: Wilson, K.P.]]
+[[Category: Wilson, K P.]]
 [[Category: ANP]]
 [[Category: MG]]
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 [[Category: phosphorylation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:36:22 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:07:36 2008''